Water → 1-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carbonitrile

HRID 1749583노트

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HRID 1749583 반응식
Br[C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=3[Cl:20])[C:6]=2[CH:5]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH:3]=1.O.[CH3:28][N:29](C=O)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2].[Zn]>[Cl:20][C:14]1[C:15]([Cl:19])=[CH:16][CH:17]=[CH:18][C:13]=1[CH2:12][N:7]1[C:6]2[CH:5]=[C:4]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[CH:3]=[C:2]([C:28]#[N:29])[C:10]=2[N:9]=[C:8]1[CH3:11]

참가 물질

8

반응물 3

HCID 962WaterHCID 6228DimethylformamideHCID 669767924-(4-bromo-1-(2,3-dichlorobenzyl)-2-methyl-1H-benzo[d]imidazol-6-yl)morpholine

생성물 1

HCID 569596841-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carbonitrile수율 45%

시약·촉매·용매 4

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 23994Zinc촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매

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온도
100 °C

실험 절차

A mixture of 4-bromo-1-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole (1 g, 2.2 mmol), Pd(dba)2 (161 mg, 0.22 mmol), dppf (244 mg, 0.44 mmol), Zn(CN)2 (1030 mg, 8.8 mmol), water (1 mL), Fe(OAc)2 (191 mg, 1.1 mmol) and Zn powder (429 mg, 6.6 mmol) in DMF (50 mL) was stirred at 100° C. under N2 for 20 h. When TLC showed no starting material remaining, the reaction mixture was quenched with water and extracted with EtOAc (100 mL×3). The organic layer was washed with brine, dried over MgSO4, concentrated. The resulting residue was purified by silica gel chromatography eluted with EtOAc to give the product (400 mg, 45%), as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.43 (s, 3H), 3.11 (t, 4H, J=4.8 Hz), 3.72 (t, 4H, J=4.8 Hz), 5.60 (s, 2H), 6.30 (dd, 1H, J=1.2, 8.1 Hz), 7.25 (t, 1H, J=8.1 Hz), 7.35 (d, 1H, J=2.1 Hz), 7.42 (d, 1H, J=2.1 Hz), 7.60 (dd, 1H, J=1.2, 8.1 Hz); LC-MS: m/e=401 [M+1]+.

후처리

  1. customthe reaction mixture was quenched with water
  2. extractionextracted with EtOAc (100 mL×3)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe resulting residue was purified by silica gel chromatography
  7. washeluted with EtOAc

출처 및 근거

ORD 기록
ord-26fca8a52f1e4fb6a443bfde1a0d46b6
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156797B2

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